Heart valve disease is a serious health problem facing society today. There are approximately 225,000 surgeries annually to repair damaged heart valves. Of these surgeries, at least 60,000 Americans receive replacements for valves damaged by congenital or rheumatic heart disease.
Cardiac valves have three functional properties: (1) preventing regurgitation of blood flow (also referred to as retrograde flow, or backflow) from one chamber to another, (2) permitting rapid flow of blood without imposing resistance on that flow, and (3) withstanding high-pressure loads. Importantly, all four of the heart valves are passive structures in that they do not themselves expend any energy and do not perform any active contractile function. They consist of movable leaflets that are designed simply to open and close in response to differential pressures on either side of the valve. Fluid flows from areas of high pressure to areas of low pressure. In the heart, the valves open and close in response to pressure gradients; that is, valves open when pressure in the preceding chamber is higher and close when the gradient reverses.
Because proper valve function is an important aspect of the present disclosure, basic cardiac physiology will be described in some detail with reference to FIGS. 1 and 2. FIG. 1 shows a cross-sectional cutaway depiction of a normal human heart 91. The left side of the heart 91 contains left atrium 93, left ventricular chamber 95 positioned between left ventricular wall 97 and septum 99, aortic valve 101, and mitral valve assembly 103. The components of the mitral valve assembly 103 include the mitral valve annulus 105, anterior leaflet 107 (sometimes referred to as the aortic leaflet, since it is adjacent to the aortic region), posterior leaflet 109, two papillary muscles 111 and 113, and multiple chordae tendineae 115. The papillary muscles 111 and 113 are attached at their bases to the interior surface of the left ventricular wall 97. The chordae tendineae 115 couple the mitral valve leaflets 107 and 109 to the papillary muscles 111 and 113, and these cords support the mitral valve leaflets and control or restrict leaflet motion.
The right side of the heart contains the right atrium 121, a right ventricular chamber 123 bounded by right ventricular wall 125 and septum 99, and a tricuspid valve assembly 127. The tricuspid valve assembly 127 comprises a valve annulus 129, three leaflets 131, papillary muscles 133 attached to the interior surface of the right ventricular wall 125, and multiple chordae tendineae 135. The chordae tendineae 135 couple the tricuspid valve leaflets 131 to the papillary muscles 133 and serve similar function as for the mitral valve leaflets.
Turning to the two cardiac valves that function to permit blood flow out of the heart to the lungs (the pulmonary valve) or to the aorta (aortic valve), reference will now be made to FIG. 2. FIG. 2 shows a cross-sectional cutaway depiction of a normal heart 91, illustrating the four valves of the heart, namely the mitral valve assembly 103, tricuspid valve assembly 127, pulmonary valve 151, and aortic valve 161. The aortic valve 161 and pulmonary valve 151 are referred to as semilunar valves because of the unique appearance of their leaflets, which are more aptly termed cusps and are shaped like a half-moon. Each of the semilunar valves includes three cusps, and neither of the valves includes associated chordae tendineae or papillary muscles.
The aortic valve includes cusps 163, 165, and 167 that respond to pressure differentials between the left ventricle and the aorta. When the left ventricle contracts, the aortic valve cusps 163, 165 and 167 open to allow the flow of oxygenated blood from the left ventricle into the aorta. When the left ventricle relaxes, the aortic valve cusps reapproximate to prevent the blood that has entered the aorta from leaking (regurgitating) back into the left ventricle. The pulmonary valve includes cusps 153, 155, and 157 that respond passively in the same manner in response to relaxation and contraction of the right ventricle in moving de-oxygenated blood into the pulmonary artery and thence to the lungs for re-oxygenation.
The valves in the heart thus maintain the physiologic direction of blood flow, namely: right atrium-right ventricle-lungs-left atrium-left ventricle-aorta. Although each of these valves has slightly different structure, they serve similar functions. When the ventricle expands, the atrioventricular valve allows blood to flow forward from the atrium into the ventricle while the semilunar valve keeps blood that has already been pumped out of the heart from flowing back in. Conversely, when the ventricle contracts, the atrioventricular valve closes to prevent backflow while the semilunar valve opens to allow blood to be pumped either to the body or the lungs. The prevention of backflow ensures the proper direction of flow through the circulatory system and reduces the amount of work the heart must do to pump blood through the system.
There are numerous complications and diseases of the heart valves that can prevent the proper flow of blood. Heart valve disease can be classified into one of two categories: stenosis (or hardening of the valve), and incompetence (or permittence of backflow). Stenotic valves cannot open fully, requiring more work to push the liquid through the valve. By contrast, incompetent valves waste work by allowing blood to flow backward (backflow). As a result of stenosis or incompetence, the heart must work harder to provide the same level of blood circulation, and in many cases the heart becomes incapable of sustaining an active lifestyle.
Though the causes of heart valve disease are numerous, there are three principal culprits. Rheumatic fever stiffens valve tissue, causing stenosis. Congenitally defective valves do not form properly as the heart develops, but often go unnoticed until adulthood. Bacterial infection of the heart can cause inflammation of valves, tissue scarring, or permanent degradation. Many of these damaged valves have to be replaced in order for the patient to live a normal life, since the strain on their heart would otherwise cause such symptoms as chest pain, fatigue, shortness of breath, and fluid retention.
Once a cardiac valve is damaged, treatment options include replacement of the damaged valve or pharmacologic intervention. Current options for replacing heart valves include mechanical prosthetics, bioprosthetics, and transplants. While each of these options has benefits, there are drawbacks associated with each.
Mechanical prosthetic heart valves mimic the function of natural heart valves with a variety of artificial structures. The majority of current mechanical valve designs, and those that are considered closest to native valves, constitute bileaflet valves. These valves consist of two semicircular leaflets (often fabricated from carbon) that pivot on hinges. The carbon leaflets exhibit high strength and excellent biocompatibility. The leaflets open completely, parallel to the direction of blood flow. However, the mechanical leaflets do not close completely, which allows some backflow. Since backflow is one of the properties of defective valves, the bileaflet valves are still not ideal valves. As a result of the less-than-ideal flow properties of the valve, these valves can cause the heart to work harder to pump blood. The resulting stress on the heart can damage heart muscle and blood cells in the vicinity of the valve. In addition, mechanical valves can cause thrombosis, or blood clot formation, and serve as excellent substrates for bacterial infection. Thus, recipients of these medical valves are often required to take anticoagulants, or blood clot inhibitors, for the rest of their lives.
Although effective for short relatively short periods (typically ten to fifteen years), bioprosthetic valves offer a second alternative for successfully replacing human valves. Generally, bioprosthetic valves are valves made from tissue harvested from other mammals. The most commonly used animal tissues for bioprosthetic valves are porcine (pig) and bovine (cow) pericardial tissue. The harvested porcine or bovine tissue is treated with a fixative (often glutaraldehyde) before implantation. The most common cause of bioprosthesis failure is stiffening of the tissue due to the build up of calcium. Calcification can cause a restriction of blood flow through the valve (stenosis) or cause tears in the valve leaflets, thereby requiring a subsequent valve replacement. Further, bioprosthetics generally do not integrate well with the host organism and eventually die.
The third alternative is a transplant from a human organ donor. In this case, the replacement valve becomes a living part of the surrounding heart tissue, if it can overcome the initial immune system rejection seen in all human-to-human transplants. However, this alternative is not commonly seen, since most available human hearts are directed to whole-heart transplants, rather than valve-only transplants.
The alternative to replacement of the damaged valve is treatment of the valve with therapeutic agents. Delivery of a therapeutic agent to the valve tissue can result in improved valve function, and correspondingly, improved heart function. Generally, pharmacologic treatment is systemic. That is, a therapeutic agent is orally or intravenously injected into the patient and is therefore delivered throughout the patient's entire body. In the case of systemic treatment, high concentrations of the therapeutic agent cannot be used in many cases, because of risk of undesirable side effects.
Thus, current treatment options for heart valve disease have several drawbacks. Damaged or diseased heart valves can be replaced with one of several different types of prosthetic valves. These prosthetic valves must create a non-return flow system and must meet certain standards with regard to strength and durability, since the human body is a harsh place for foreign objects. Alternatively, damaged or diseased heart valves can be treated with therapeutic agents. Although therapeutic treatment is a preferred alternative to outright replacement of the valve, risks associated with systemic exposure to the therapeutic agent(s) must be taken into consideration.
For treating vessel walls, a flow through catheter has been developed that merely provides flow through while exposing the vessel walls to a therapeutic agent. U.S. Pat. No. 5,558,642 (the entire disclosure of which is incorporated herein by reference) describes a drug delivery catheter that can be inserted into a vessel, such as a blood vessel. The drug delivery catheter comprises an elongated tubular shaft that includes a drug lumen for delivering a drug to the treatment site and a uniquely configured inflatable balloon assembly. The balloon assembly is disposed at the distal end of the shaft and includes an inflatable balloon member. The balloon member has a configuration such that when the balloon member is uninflated, the fluid in the vessel (such as blood) may flow around the balloon assembly. This provides an arrangement that may be easily inserted and manipulated through the vascular system. When the balloon member is in an inflated state, part of the balloon member contacts the vessel wall defining a containment pocket between the vessel wall and the balloon assembly. The balloon assembly includes apertures in the containment pocket that are in fluid communication with a drug lumen in order to provide the drug to the containment pocket. A flow lumen is also defined through the balloon member when it is inflated in order to allow the fluid in the vessel, such as blood, to flow through the balloon assembly. The catheter also includes an inflation lumen that is used to inflate the balloon member.